Methyl iodide → 2-Fluoro-5-methoxy-4-methylbenzoic acid

HRID 446273Notes

Reaction equation

[CH3:1]C(C)([O-])C.[K+].[F:7][C:8]1[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[CH:13][C:9]=1[C:10]([OH:12])=[O:11].C([Li])CCC.IC>C1COCC1>[F:7][C:8]1[CH:16]=[C:15]([CH3:1])[C:14]([O:17][CH3:18])=[CH:13][C:9]=1[C:10]([OH:12])=[O:11]

Participants

Conditions

Temperature: -78 °C

Procedure

Potassium tert-butoxide (7.92 g, 70.5 mmol) was dissolved in THF (150 mL) and cooled to −78° C. 2-Fluoro-5-methoxybenzoic acid (3.00 g, 17.6 mmol) in THF (100 mL) was added followed by n-butyl lithium (2.5 N in hexanes, 28.2 mL, 70.5 mmol). After 40 minutes, iodomethane (2.2 mL, 35.4 mmol) was added and allowed to stir at −78° C. for 70 minutes before warming to room temperature. The reaction was quenched with saturated ammonium chloride (100 mL) and extracted with ether. The aqueous layer was acidified using 6 N HCl then extracted with ether. The organic layer was dried over sodium sulfate, filtered and concentrated. The crude material was purified by Gilson reverse-phase HPLC (acidic mobile phase) to yield 2-fluoro-5-methoxy-4-methylbenzoic acid as a white solid. MS m/z=185 [M+1]+. Calc'd for C9H9FO3: 184.20.

Workup

temperaturebefore warming to room temperature
customThe reaction was quenched with saturated ammonium chloride (100 mL)
extractionextracted with ether
extractionthen extracted with ether
dry with materialThe organic layer was dried over sodium sulfate
filtrationfiltered
concentrationconcentrated
customThe crude material was purified by Gilson reverse-phase HPLC (acidic mobile phase)

Sources & evidence

ORD record: ord-b892d61728044880aa56bbe24bd159bf
Source dataset: uspto-grants-2013_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08476434B2

Reaction notes

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